This application entitled Development of a Silk-Stabilized Inactivated Polio Vaccine is a response to the Omnibus solicitation of the National Institutes of Health, Centers for Disease Control and Prevention, Food and Drug Administration, and Administration for Children and Families for Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grant Applications, PHS 2014-2. In this proposal, we seek to address a critical outstanding need for a robust, thermally stable inactivated polio vaccine (IPV) that will benefit the global effort to eradicate polio and meet pos-eradication immunization needs. Current IPV products are sensitive to both freezing and elevated temperatures and therefore must be shipped and stored between 2 and 8 C, a requirement that imposes financial and logistical challenges in the global distribution of IPV. A thermostable IPV formulation would simplify access in areas of the world that lack sufficient cold-chain capacity and decrease cold-chain-associated costs for vaccine manufacturers, national governments, and non-profit vaccine buyers. We will focus on stabilization of poliovirus antigens using a novel approach based on silk. Specifically, we aim to identify lead-candidate liquid and solid formulations of a silk-IPV complex with improved stability and equivalent immunogenicity compared to the existing commercial IPV formulation. Through the proposed research, we expect to gain a deeper fundamental understanding of silk-vaccine interactions that will guide formulation development. Furthermore, we expect to gain a better understanding of the immunogenicity of the silk protein itself as well as the impact of silk protein on the immunogenicity of poliovirus antigens. These insights are crucial to establish proof-of-concept and advance the technology into Phase II studies. Successful stabilization of IPV would not only have significant positive impact on global polio immunization efforts, but may also revolutionize the broader approach to vaccine development and distribution.